Indane

Abstract: Enantioselective trifluoromethylthiolation, especially of alkenes, is a challenging task. In this work, we have developed an efficient approach for enantioselective trifluoromethylthiolating lactonization by designing an indane-based bifunctional chiral sulfide catalyst and a shelf-stable electrophilic SCF3 reagent. The desired products were formed with diastereoselectivities of >99:1 and good to excellent enantioselectivities. The transformation represents the first enantioselective trifluoromethylthiolation of alkenes and the first enantioselective trifluoromethylthiolation that is enabled by a catalyst with a Lewis basic sulfur center.

Abstract: The oxindole framework is a motif common to natural products and pharmaceutically active compounds. In particular, 3,3-disubstituted oxindoles have shown promising biological activity. Considerable efforts have been dedicated to developing new methods for the preparation of these pharmacaphores, especially spiro-oxindoles: functionalization of heterocycles, variations of the Stolle reaction, epoxide rearrangement, Lewis acid promoted cyclization, Pummerer rearrangement, and various palladium-catalyzed methodologies. Within that last category, the intramolecular Heck reaction is of particular relevance here. Although tremendous efforts have been invested in the discovery of new palladium-catalyzed processes, there remains limited overlap between two key transformations, namely the Heck reaction and the direct arylation reaction, which appear to be orthogonal methodologies. Most relevant examples of reaction commonality entail carbopalladation to form a vinylpalladium intermediate and subsequent C H functionalization. The two examples that proceed by olefin insertion to form an alkylpalladium intermediate undergo C H insertion to form a cyclobutane product after reductive elimination. Of particular relevance to this work is the report from Grigg et al. on a Heck reaction that forms an alkylpalladium complex and then undergoes a heteroatom-directed arylation reaction to make a fivemembered ring. Herein we report an efficient preparation of spiro-fused indane-oxindoles by carbopalladation to form an alkylpalladium intermediate and subsequent functionalization of an unactivated aryl C H bond. (Scheme 1). To investigate the viability of a tandem Heck/arylation reaction sequence, we prepared N-(2-bromophenyl)acrylamides (5a–h) in a five-step sequence from 2-bromoaniline (1) (Scheme 2). Reductive amination between p-anisaldehyde and 2-bromoaniline afforded PMB-protected aniline 2 (PMB= p-methoxybenzyl). Amide bond formation between compound 2 and potassium mono-methyl malonate provided malonamic acid methyl ester 3, which was alkylated with the requisite substituted benzyl bromide to afford alkylation products 4a–h. Hydrolysis of the methyl ester, and treatment of the liberated carboxylic acid with diethylamine and paraformaldehyde, furnished acrylamides 5a–h in good yields. Initial efforts to effect the desired transformation from compound 5a to 6a employed the catalytic system reported by Fagnou and co-workers: Pd(OAc)2 (10 mol%), PtBu3HBF4 (20 mol%), and K2CO3 in DMA at 130 8C. [15,17] Gratifyingly, spiro-fused indane-oxindole 6a was observed under these conditions. A second product (7; see Scheme 4), assigned as the product formed by a reductive Heck reaction, was also observed in the complex reaction mixture. A series of palladium sources and ligands was screened in an effort to develop a cleaner reaction. Decreasing the catalyst loading in Scheme 1. Heck/C H functionalization tandem reaction. PMB=pmethoxybenzyl.

Abstract: Two highly stereoselective radical-mediated syntheses of densely functionalized indanes and dibenzocycloheptadienes from ortho-vinyl- and ortho-vinylaryl-substituted N-(arylsulfonyl)-acrylamides, respectively, are presented here. The chemoselective addition of in situ generated radicals (X.) onto the styrene moieties triggers an unprecedented reaction cascade, resulting in the formation of one new CX bond and two new CC bonds, a formal 1,4-aryl migration, and the extrusion of SO2 to generate an amidyl radical intermediate. This intermediate, upon H abstraction, leads to the observed 5- and 7-membered ring carbocyclic products, respectively, in a highly efficient manner.